Combination of a big-h3 antagonist and an immune checkpoint inhibitor for the treatment of solid tumor

Abstract

To study the mechanism of βig-h3 modulation of the anti-tumoral immune response in pancreatic cancer, Inventors took advantage of engineered mouse models of spontaneous pancreatic neoplasia and cancer to evaluate the effect of depleting βig-h3 on the modulation of anti-tumor immunity and its subsequent impact on tumour growth alone and in combination with an immune checkpoint inhibitor. This association proved to be effective in vivo in this model showing a synergic effect of the therapeutic combination. Accordingly, the present invention relates to a combination of (i) an immune checkpoint inhibitor, and (ii) a βig-h3 antagonist, for simultaneous or sequential use in the treatment of a patient suffering from solid tumor, e.g. a pancreatic cancer. The present invention also provides a βig-h3 antagonist, for use in a method for enhancing sensitivity of a patient suffering from a solid tumor to an immune checkpoint inhibitor.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a combination of (i) a βig-h3 antagonist, and (ii) an immune checkpoint inhibitor, for the simultaneous or sequential use in the treatment of a patient suffering from a solid tumor, e.g. a pancreatic cancer. The present invention also provides a βig-h3 antagonist, for use in a method for enhancing sensitivity of a patient suffering from tumor to an immune checkpoint inhibitor.BACKGROUND OF THE INVENTION[0002]Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive cancer with a median survival of less than 6 months and a 5-year survival rate of 3-5%1. PDA evolves through a series of pancreatic intraepithelial neoplasias (PanINs) that are accompanied by genetic modifications. Of these, the earliest and most ubiquitous is the oncogenic activation of Kras2. In addition to the molecular and histological alterations that define cancer cells, a hallmark of PDA is the prominent stromal reaction that surrounds the neoplastic ...

AI Technical Summary

Benefits of technology

The patent describes a new way to treat pancreatic cancer using a combination of immune checkpoint inhibitors and a stromal target called βig-h3. This combination therapy was more effective than using either treatment alone and could allow for lower doses of the immune checkpoint inhibitors. The researchers showed that neutralizing βig-h3 made it easier for anti-tumor T cells to release mechanical tension and penetrate the cancer cells. This suggests that targeting stromal targets like βig-h3 could enhance the response to immunotherapy and improve treatment outcomes for pancreatic cancer and other solid tumors.

Problems solved by technology

Immune checkpoint blockade has elicited clinical responses in some patients with different advanced malignancies (ie melanoma) but has not been effective in PDAC, suggesting that other factors including mechanical tension generated in desmoplastic tumor microenvironment may limit T cell activity10.

To conclude, Immune checkpoint blockade have been tested as anticancer therapy but have not proven liable to completely treat all individuals afflicted with cancer, and especially solid tumors such as pancreatic cancers, which are notably associated with poor prognosis.

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